Epilepsy Flashcards
Na and Ca channels
6 membrane spanning regions x 4
-B subunit regulates function
K channels
- 6,2,4, or 7 membrane spanning regions
- voltage sensor
seizure
- abnormal excessive and synchronous electrical discharges of brain neuronal network
- leading to paroxysmal events characterized by clinical signs/symptoms
aura
- ictal
- part of seizure
- symptoms hard to define
- sense that one is coming
prodrom
- pre-ictal
- sensation that it’s coming/ other symptoms
ictal
seizure period/ events due to seizure
interictal
-b/n 2 seizures, no symptoms
post ictal
-hypoactive right after seizure
partial seizures
- one hemisphere
- simple doesn’t alter consciousness, complex does
- both can progress to secondary generalized
generalized seizures
-convulsive or not
partial seizures 2
A. simple- with motor, somatosensory, special, autonomic, psychic
B complex- simple partial onset followed by impaired consciousness, or can start with impaired
C. evolving-simple, complex, or simple to complex to generalized
generalized 2
A. Absence seizures- typical, atypical (behavior arrest) B myoclonic C clonic D tonic E tonic-clonic F atonic G unclassified
epilepsy
disease of the brain characterized by enduring predisposition to generate epileptic seizures
epilepsy syndrome
- electroclinical syndrome
- complex of clinical features, signs and symptoms that together define a distinctive, recognizable clinical disorder
idiopathic
genetic
symptomatic
known or suspected disorder of CNS
cryptogenic
unknown cause
epileptic channelopathies
- lowered seizure threshold based on a mutation causing changes in the current carried by the channel
- enhanced of reduced function
- majority AD and de novo
a subunit of Na channel
- 9 variations
- Nav1.1, 1.2, 1.3, 1.6 encoded by SCN1A, 2A, 3A, 8A
- mostly in CNS
- 1.1 and 1.3 in cell bodies
- 1.2 in unmyelinated axons and dendrites
1. 6 in myelinated
severe myoclonic epilepsy of infancy
-SMEI or Dravet syndrome
1st year- seizures associated with elevated body temp (fever or bathing)
-progressively prolonged and cluster seizures
-status epilepticus
2nd year- psychomotor delay
-ataxia, cognitive impairment
-both caused by reduction of Na channel density, loss of high frequency AP and loss of inhibitory function of GABA in interneurons and then purkinje cells
-treat by re-establishing GABA action-decrease reuptake or increase response of post synapse- tiagabine and clonazepam
generalized epilepsy with febrile seizures plus
- milder than SMEI
- usually no cognitive impairment
- first mutation found in SCN1B encoding B1 subunit
- later SNC1A mutations were found
- missense mutations cause loss of function of fast inactivation–>gain of function of Na channels–>persistant Na current
- trt-antepileptic meds that can bind to mutant channels and stabilize folding of proteins
febrile seizures
- seizure occurring in childhood after 1 month of age
- associated with a febrile illness not caused by and infection of the CNS
- without previous neonatal seizures of a previous unprovoked seizure
- and not meeting criteria for other acute symptomatic seizures
- mutations in Nav1.1
- reduction in peak Na currents
- positive shift in voltage dependence of activation
Nav1.1 mutations
- missense-febrile, mild/moderate
- missense moderate/severe- GEFS+
- truncation/loss of function-SMEI
K channelopathies
- Kv 7.2 and 7.3 subunit encoded by KCNQ2 and Q3
- mostly in cells with M current- close to resting potential and regulated by muscarinic and other G protein coupled receptors
- missense mutation-impaired flux of K-loss of function–>decreased M current
- benign familial neonatal convulsion- normal development and behavior, brief generalized and partial seizures, resolves by age 6 weeks
k channelopathy 2
- pore forming subunit-encoded by KCNMA1
- mutation-more influx of K, generalized epilepsy and paroxysmal dyskinesia
Ca channelopathy
- T type
- can have rhythmic burst firing because:
- activated with small depol
- inactivated with maintained depol
- cycle continues
- mostly in thalamic cells
- Cav3.1, 3.2, 3.3- CACNA1G, 1H, 1I
- mutations-gain of function-excessive synchronous rhythmic burst firing, idiopathic generalized epilepsy
Cl channelopathies
- 12 trans membrane segments
- maintain the Cl gradient required for GABA synapses hyperpolarization
- mutations in CLCN2 gene can lead to idiopathic generalized epilepsy
treatment
- anti-epileptic drugs
- decrease hyperexcitability, Na channel blockers, increasing GABA
- surgery
- not all seizures are channelopathies
- surgery may be considered in localization related epilepsy that is medically refractory
- fail to respond to 2 meds
- if seizure onset zone can be identified and is not in eloquent cortex
AEDs and ion channels
- mechanism of action of a large group of AEDs is stabilizing or blocking Na channels
- prevent return of the channels to the active state by prolonging the inactive state
